Zollinger-Ellison Syndrome – Causes, Symptoms, Treatment

Acid production in the stomach is a carefully controlled process. It needs to be sufficient to aid in chemical digestion of food but too much of acid can also cause problems. Stomach acid levels fluctuate depending on meals and time of the day. These fluctuations are considered normal. However, there are some conditions where the stomach acid levels may be abnormally high due to overstimulation of the acid-producing cells of the stomach.

What is Zollinger-Ellison syndrome?

Zollinger-Ellison syndrome is a condition where there is excessive stomach acid secretion due to tumors in the pancreas. These tumors are known as gastrinomas because it produces the hormone gastrin. This hormone stimulates the acid-producing cells of the stomach wall. Therefore the stomach acid production increases substantially and complications of high stomach acid levels then arises.

Overall Zollinger-Ellison syndrome is a rare condition. It occurs in about 1 in 100 people with duodenal ulcers and is only slightly more prevalent in males than females. Zollinger-Ellison syndrome can be effectively treated and the progonosis is usually good unless the tumor is malignant and has spread. Treatment involves a combination of both medication and surgery.

Causes of Zollinger-Ellison Syndrome

The exact cause of Zollinger-Ellison syndrome is unclear. It starts with a gastrinoma so the cause of gastrinomas needs to be considered. However, the exact reason why gastrinomas arise is also not known. Thes tumors, which may be benign (non-cancerous) or malignant (cancerous), may occur due to genetic factors or exposure to carcinogens (cancer-causing substances). However, most of the time the exact cause of a gastrinoma cannot be identified.

These tumors may occur on its own or be associated with multiple endocrine neoplasia (MEN) type 1. This is an inherited condition where tumors may occur in glands. These tumors may occur in multiple glands at the same time. Gastrinomas can occur at various sites but is more common in the pancreas. This is a gland that is located next to the stomach. Gastrinomas are also commonly found on the duodenumal wall, which also lies next to the stomach.

Gastrin and Stomach Acid

Gastrin is a hormone that is secreted by certain cells in the stomach, duodenum (first part of the small intestine) and pancreas. This hormone stimulates the production of hydrochloric acid (HCl) in the stomach. It also stimulates movement in the stomach by the activity of the muscles in the stomach wall. A feedback mechanism ensures that gastrin is secreted when stomach acid is low in order to stimulate the stomach to produce more acid.

With the high levels of gastrin in the blood (hypergastrinemia) there may also be tissue changes in the stomach wall. There is an increase in the cells that produce hydrochloric acid (HCl) due to the elevated gastrin levels. More parietal cells that produce acid increases stomach acid production. In addition the gastrin itself stimulates these cells to produce acid at its maximum capacity.

Excess Acid in the Gut

The stomach has a mucus barrier that protects the wall from the acid. However, when the quantity of acid within the stomach is excessive then even this barrier cannot entirely prevent acid contact with the stomach wall. As a result it may lead to conditions like stomach ulcers. The consequences are not limited to the stomach only. The surrounding parts of the digestive tract, like the esophagus and the duodenum (small intestine), may also be involved.

Ulcers are more likely to occur in the duodenum as it lacks the same mucus barrier as the stomach to protect it from the high levels of the acid. Duodenal mechansims to dilute and neutralize the acid may be insufficient in the backdrop of the elevated acid levels. Irritation and injury of the other parts of the gut by the acid in addition to increased motility can also affect absorption of nutrients (malabsorption) and lead to diarrhea.

Signs and Symptoms

The signs and symptoms of Zollinger-Ellison syndrome are due to the consequences of increased gastrin levels. This results in increased stomach acid levels and increased movement through the stomach (gastric motility). These signs and symptoms are similar to gastritis and peptic ulcers due to other more common causes. It is therefore difficult to conclusively attribute these symptoms to Zollinger-Ellison syndrome.

Stomach pain – upper left region of the abdomen and is often described as a burning pain or dull gnawing ache.

Abdominal pain or cramps – diffuse throughout the abdomen.

Heartburn – burning chest pain due to acid reflux.

Nausea with or without vomiting.

Bleeding from the ulcers.

Reduced appetite.

Diarrhea.

Unintentional weight loss.

Other symptoms may arise as a result of complications. Persistent gastrointestinal bleeding may result in anemia and this may in turn present with paleness of the skin. Similarly persistent and severe acid reflux can affect the teeth and result in dental erosions over time.

Treatment of Zollinger-Ellison Syndrome

Zollinger-Ellison has to be diagnosed with various investigations. The symptoms alone are not conclusive for Zollinger-Ellison syndrome as most of the symptoms are present with peptic ulcers due to other causes, like H.pylori infection or with the excessive use of NSAIDs. Blood tests will confirm the elevated gastrin levels and imaging tests (scans) using radioactive tracers can help in locating the gastrin-producing tumor.

The first goal of treatment in Zollinger-Ellison syndrome is to control the secretion of stomach acid. Certain drugs can impair the acid-producing process thereby counteracting the acid hypersecretion. Once this is achieved then the gastrin-producing tumor needs to be surgically removed. Complications like gastrointestinal bleeding may also require treatment although these conditions often resolve once the tumor is successfully removed.

Proton pump inhibitors (PPIs) are acid-suppressing drugs that counteract the hypersecretion of stomach acid. However, excessive use of PPIs can also increase gastrin levels.

Octreotide is a drug that can counteract the effects of gastrin by acting similar to the hormone somatostatin. This hormone inhibits stomach acid secretion.

Resection is the surgical removal of the gastrin-secreting tumor which should result in a normalization of gastrin levels. However, this can be difficult to acbieve when there are multiple tumors secreting gastrin.

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